Glucose 6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme in the pentose phosphate pathway, appears to be subject to neurotrophic regulation in skeletal muscle. The activity of muscle G6PD increases markedly following denervation. We propose to investigate the mechanism underlying increase. Specifically, we will (a) study the relative roles of axonally derived trophic factors and neuromuscular activity, (b) study a possible modulatory role of androgens in neural influences, (c) compare properties of G6PD from normal and denervated muscle; and, (d) determine whether the increase in G6PD represents enzyme induction. The information gained from these studies will contribute to our understanding of neuronal regulation of muscle properties and may advance our knowledge of the pathogenesis of human motoneuron diseases, such as amyotrophic lateral sclerosis (ALS).